Donald Kirsten A, Wedderburn Catherine J, Barnett Whitney, Hoffman Nadia, Zar Heather J, Redei Eva E, Stein Dan J
Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Front Endocrinol (Lausanne). 2018 Jun 5;9:294. doi: 10.3389/fendo.2018.00294. eCollection 2018.
Fetal alcohol spectrum disorders (FASD) have an estimated global prevalence of 2-5% of births, but prevalence is reported to be as high as 15.5% for FASD in certain high-risk communities in South Africa. Preclinical studies demonstrate that alcohol consumption during pregnancy interferes with thyroid hormone availability and function and negatively impacts exposed offspring. Very little is currently reported on this phenomenon in humans.
This pilot study was embedded in the Drakenstein Child Health Study, a multi-disciplinary longitudinal birth cohort study investigating the early biological and psychosocial determinants of child health in South Africa. Twenty one mothers and their children with moderate-severe prenatal alcohol exposure (PAE) and 19 mothers and their children with no alcohol exposure were investigated. Maternal exposure history and blood samples were collected in mid-pregnancy and analyzed for serum-free thyroxin (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH). Children were assessed with formally measured growth parameters and development was evaluated using the Bayley III Scales of Infant and Toddler Development (BSID III) at 6 and 24 months of age.
While there were no significant differences in serum TSH and FT4 between groups, FT3 levels were significantly higher in mothers with moderate-severe prenatal alcohol use. In abstinent pregnant women, levels of FT4 were significantly correlated with infants' scores on cognitive measures at 6 and 24 months of age and with levels of gross motor skills at 24 months. However, in mothers with alcohol use, FT4 levels were not correlated with any cognitive or motor skills, but FT3 levels were significantly associated with scores on children's social-emotional development at 24 months of age.
Thyroid function in PAE is sufficiently disrupted to lead to alterations in serum FT3 levels. The contrast in findings between PAE and abstinent dyads in their association of maternal thyroid function and infant development further suggests that such disruption is present and may contribute to adverse neurodevelopment. Further work is needed to determine the relationship between peripheral thyroid indices during pregnancy and neurodevelopmental outcomes in the context of PAE.
胎儿酒精谱系障碍（FASD）在全球出生人口中的估计患病率为2%-5%，但据报道，在南非某些高风险社区，FASD的患病率高达15.5%。临床前研究表明，孕期饮酒会干扰甲状腺激素的可利用性和功能，并对受影响的后代产生负面影响。目前关于人类这一现象的报道非常少。
这项试点研究纳入了德拉肯斯堡儿童健康研究，这是一项多学科纵向出生队列研究，旨在调查南非儿童健康的早期生物学和社会心理决定因素。研究了21名有中度至重度产前酒精暴露（PAE）的母亲及其子女，以及19名无酒精暴露的母亲及其子女。在孕中期收集母亲的暴露史和血样，分析血清游离甲状腺素（FT4）、游离三碘甲状腺原氨酸（FT3）和促甲状腺激素（TSH）。对儿童进行正式测量的生长参数评估，并在6个月和24个月大时使用贝利婴幼儿发展量表第三版（BSID III）评估发育情况。
虽然两组之间血清TSH和FT4没有显著差异，但中度至重度产前饮酒的母亲的FT3水平显著更高。在戒酒的孕妇中，FT4水平与婴儿6个月和24个月大时的认知测量得分以及24个月大时的大运动技能水平显著相关。然而，在饮酒的母亲中，FT4水平与任何认知或运动技能均无相关性，但FT3水平与儿童24个月大时的社会情感发展得分显著相关。
PAE中的甲状腺功能受到充分干扰，导致血清FT3水平改变。PAE组和戒酒组在母亲甲状腺功能与婴儿发育关联方面的研究结果对比进一步表明，这种干扰存在，可能导致不良神经发育。需要进一步开展工作，以确定孕期外周甲状腺指标与PAE背景下神经发育结局之间的关系。
